1ao8 - Revision history

OCA at 08:14, 22 May 2024

OCA — Wed, 22 May 2024 08:14:47 GMT

←Older revision		Revision as of 08:14, 22 May 2024
Line 20:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ao8 ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ao8 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We have determined the three-dimensional solution structure of the complex of Lactobacillus casei dihydrofolate reductase (18.3 kDa, 162 amino acid residues) formed with the anticancer drug methotrexate using 2531 distance, 361 dihedral angle and 48 hydrogen bond restraints obtained from analysis of multidimensional NMR spectra. Simulated annealing calculations produced a family of 21 structures fully consistent with the constraints. The structure has four alpha-helices and eight beta-strands with two other regions, comprising residues 11 to 14 and 126 to 127, also interacting with each other in a beta-sheet manner. The methotrexate binding site is very well defined and the structure around its glutamate moiety was improved by including restraints reflecting the previously determined specific interactions between the glutamate alpha-carboxylate group with Arg57 and the gamma-carboxylate group with His28. The overall fold of the binary complex in solution is very similar to that observed in the X-ray studies of the ternary complex of L. casei dihydrofolate reductase formed with methotrexate and NADPH (the structures of the binary and ternary complexes have a root-mean-square difference over the backbone atoms of 0.97 A). Thus no major conformational change takes place when NADPH binds to the binary complex. In the binary complex, the loop comprising residues 9 to 23 which forms part of the active site has been shown to be in the "closed" conformation as defined by M. R. Sawaya & J. Kraut, who considered the corresponding loops in crystal structures of complexes of dihydrofolate reductases from several organisms. Thus the absence of the NADPH does not result in the "occluded" form of the loop as seen in crystal studies of some other dihydrofolate reductases in the absence of coenzyme. Some regions of the structure in the binary complex which form interaction sites for NADPH are less well defined than other regions. However, in general terms, the NADPH binding site appears to be essentially pre-formed in the binary complex. This may contribute to the tighter binding of coenzyme in the presence of methotrexate.
		+
		+	The solution structure of the complex of Lactobacillus casei dihydrofolate reductase with methotrexate.,Gargaro AR, Soteriou A, Frenkiel TA, Bauer CJ, Birdsall B, Polshakov VI, Barsukov IL, Roberts GC, Feeney J J Mol Biol. 1998 Mar 20;277(1):119-34. PMID:9514736<ref>PMID:9514736</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 1ao8" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]		*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 15:26, 13 March 2024

OCA — Wed, 13 Mar 2024 15:26:29 GMT

←Older revision		Revision as of 15:26, 13 March 2024
Line 1:		Line 1:

	==DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE, NMR, 21 STRUCTURES==		==DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE, NMR, 21 STRUCTURES==
-	<StructureSection load='1ao8' size='340' side='right'caption='[[1ao8~~]], [[NMR_Ensembles_of_Models \| 21 NMR models~~]]' scene=''>	+	<StructureSection load='1ao8' size='340' side='right'caption='[[1ao8]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ao8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~"bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AO8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AO8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ao8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lacticaseibacillus_casei Lacticaseibacillus casei]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AO8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AO8 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
-	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks~~'>~~[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3]~~ </~~span~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [https://pdbe.org/1ao8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [https://www.ebi.ac.uk/pdbsum/1ao8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ao8 ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [https://pdbe.org/1ao8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [https://www.ebi.ac.uk/pdbsum/1ao8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ao8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/DYR_LACCA DYR_LACCA]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.	+	[https://www.uniprot.org/uniprot/DYR_LACCA DYR_LACCA] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 20:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ao8 ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ao8 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	We have determined the three-dimensional solution structure of the complex of Lactobacillus casei dihydrofolate reductase (18.3 kDa, 162 amino acid residues) formed with the anticancer drug methotrexate using 2531 distance, 361 dihedral angle and 48 hydrogen bond restraints obtained from analysis of multidimensional NMR spectra. Simulated annealing calculations produced a family of 21 structures fully consistent with the constraints. The structure has four alpha-helices and eight beta-strands with two other regions, comprising residues 11 to 14 and 126 to 127, also interacting with each other in a beta-sheet manner. The methotrexate binding site is very well defined and the structure around its glutamate moiety was improved by including restraints reflecting the previously determined specific interactions between the glutamate alpha-carboxylate group with Arg57 and the gamma-carboxylate group with His28. The overall fold of the binary complex in solution is very similar to that observed in the X-ray studies of the ternary complex of L. casei dihydrofolate reductase formed with methotrexate and NADPH (the structures of the binary and ternary complexes have a root-mean-square difference over the backbone atoms of 0.97 A). Thus no major conformational change takes place when NADPH binds to the binary complex. In the binary complex, the loop comprising residues 9 to 23 which forms part of the active site has been shown to be in the "closed" conformation as defined by M. R. Sawaya & J. Kraut, who considered the corresponding loops in crystal structures of complexes of dihydrofolate reductases from several organisms. Thus the absence of the NADPH does not result in the "occluded" form of the loop as seen in crystal studies of some other dihydrofolate reductases in the absence of coenzyme. Some regions of the structure in the binary complex which form interaction sites for NADPH are less well defined than other regions. However, in general terms, the NADPH binding site appears to be essentially pre-formed in the binary complex. This may contribute to the tighter binding of coenzyme in the presence of methotrexate.
-
-	The solution structure of the complex of Lactobacillus casei dihydrofolate reductase with methotrexate.,Gargaro AR, Soteriou A, Frenkiel TA, Bauer CJ, Birdsall B, Polshakov VI, Barsukov IL, Roberts GC, Feeney J J Mol Biol. 1998 Mar 20;277(1):119-34. PMID:9514736<ref>PMID:9514736</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1ao8" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]		*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bacillus a von freudenreich 1890]]~~	+	[[Category: Lacticaseibacillus casei]]
-	~~[[Category: Dihydrofolate reductase~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Barsukov~~, I L~~]]	+	[[Category: Barsukov IL]]
-	[[Category: Bauer~~, C J~~]]	+	[[Category: Bauer CJ]]
-	[[Category: Birdsall, B]]	+	[[Category: Birdsall B]]
-	[[Category: Feeney, J]]	+	[[Category: Feeney J]]
-	[[Category: Frenkiel~~, T A~~]]	+	[[Category: Frenkiel TA]]
-	[[Category: Gargaro~~, A R~~]]	+	[[Category: Gargaro AR]]
-	[[Category: Polshakov~~, V I~~]]	+	[[Category: Polshakov VI]]
-	[[Category: Roberts~~, G C.K~~]]	+	[[Category: Roberts GCK]]
-	[[Category: Soteriou, A]]	+	[[Category: Soteriou A]]
-	~~[[Category: Inhibitor-enzyme complex]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 09:47, 26 May 2021

OCA — Wed, 26 May 2021 09:47:22 GMT

←Older revision		Revision as of 09:47, 26 May 2021
Line 3:		Line 3:
	<StructureSection load='1ao8' size='340' side='right'caption='[[1ao8]], [[NMR_Ensembles_of_Models \| 21 NMR models]]' scene=''>		<StructureSection load='1ao8' size='340' side='right'caption='[[1ao8]], [[NMR_Ensembles_of_Models \| 21 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ao8]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/"bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AO8 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1AO8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ao8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AO8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AO8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [~~http~~://pdbe.org/1ao8 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1ao8 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1ao8 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [https://pdbe.org/1ao8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [https://www.ebi.ac.uk/pdbsum/1ao8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ao8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/DYR_LACCA DYR_LACCA]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.	+	[[https://www.uniprot.org/uniprot/DYR_LACCA DYR_LACCA]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 07:38, 21 August 2019

OCA — Wed, 21 Aug 2019 07:38:39 GMT

←Older revision		Revision as of 07:38, 21 August 2019
Line 1:		Line 1:

	==DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE, NMR, 21 STRUCTURES==		==DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE, NMR, 21 STRUCTURES==
-	<StructureSection load='1ao8' size='340' side='right' caption='[[1ao8]], [[NMR_Ensembles_of_Models \| 21 NMR models]]' scene=''>	+	<StructureSection load='1ao8' size='340' side='right'caption='[[1ao8]], [[NMR_Ensembles_of_Models \| 21 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ao8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AO8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AO8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ao8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AO8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AO8 FirstGlance]. <br>
Line 14:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ao/1ao8_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ao/1ao8_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 29:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 1ao8" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1ao8" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 35:		Line 38:
	[[Category: Bacillus a von freudenreich 1890]]		[[Category: Bacillus a von freudenreich 1890]]
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
		+	[[Category: Large Structures]]
	[[Category: Barsukov, I L]]		[[Category: Barsukov, I L]]
	[[Category: Bauer, C J]]		[[Category: Bauer, C J]]

OCA at 10:40, 15 November 2017

OCA — Wed, 15 Nov 2017 10:40:08 GMT

←Older revision		Revision as of 10:40, 15 November 2017
Line 1:		Line 1:
		+
	==DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE, NMR, 21 STRUCTURES==		==DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE, NMR, 21 STRUCTURES==
	<StructureSection load='1ao8' size='340' side='right' caption='[[1ao8]], [[NMR_Ensembles_of_Models \| 21 NMR models]]' scene=''>		<StructureSection load='1ao8' size='340' side='right' caption='[[1ao8]], [[NMR_Ensembles_of_Models \| 21 NMR models]]' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [http://pdbe.org/1ao8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [http://www.ebi.ac.uk/pdbsum/1ao8 PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [http://pdbe.org/1ao8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [http://www.ebi.ac.uk/pdbsum/1ao8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ao8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 28:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 1ao8" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1ao8" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:35, 9 February 2016

OCA — Tue, 09 Feb 2016 15:35:33 GMT

←Older revision		Revision as of 15:35, 9 February 2016
Line 17:		Line 17:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ao8 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 23:38, 10 September 2015

OCA — Thu, 10 Sep 2015 23:38:05 GMT

←Older revision		Revision as of 23:38, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='1ao8' size='340' side='right' caption='[[1ao8]], [[NMR_Ensembles_of_Models \| 21 NMR models]]' scene=''>		<StructureSection load='1ao8' size='340' side='right' caption='[[1ao8]], [[NMR_Ensembles_of_Models \| 21 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ao8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Lactobacillus_casei Lactobacillus casei~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AO8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AO8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ao8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AO8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AO8 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [http://www.ebi.ac.uk/pdbsum/1ao8 PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [http://pdbe.org/1ao8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [http://www.ebi.ac.uk/pdbsum/1ao8 PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 27:		Line 27:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 1ao8" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 34:		Line 35:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bacillus a von freudenreich 1890]]
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
-	[[Category: Lactobacillus casei]]
	[[Category: Barsukov, I L]]		[[Category: Barsukov, I L]]
	[[Category: Bauer, C J]]		[[Category: Bauer, C J]]

OCA at 07:46, 25 December 2014

OCA — Thu, 25 Dec 2014 07:46:37 GMT

←Older revision		Revision as of 07:46, 25 December 2014
Line 7:		Line 7:
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [http://www.ebi.ac.uk/pdbsum/1ao8 PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [http://www.ebi.ac.uk/pdbsum/1ao8 PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DYR_LACCA DYR_LACCA]] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 10:08, 22 December 2014

OCA — Mon, 22 Dec 2014 10:08:00 GMT

←Older revision		Revision as of 10:08, 22 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ao8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lactobacillus_casei Lactobacillus casei]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AO8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AO8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ao8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lactobacillus_casei Lactobacillus casei]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AO8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AO8 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene></td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [http://www.ebi.ac.uk/pdbsum/1ao8 PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [http://www.ebi.ac.uk/pdbsum/1ao8 PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 34:		Line 34:
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Lactobacillus casei]]		[[Category: Lactobacillus casei]]
-	[[Category: Barsukov, I L.]]	+	[[Category: Barsukov, I L]]
-	[[Category: Bauer, C J.]]	+	[[Category: Bauer, C J]]
-	[[Category: Birdsall, B.]]	+	[[Category: Birdsall, B]]
-	[[Category: Feeney, J.]]	+	[[Category: Feeney, J]]
-	[[Category: Frenkiel, T A.]]	+	[[Category: Frenkiel, T A]]
-	[[Category: Gargaro, A R.]]	+	[[Category: Gargaro, A R]]
-	[[Category: Polshakov, V I.]]	+	[[Category: Polshakov, V I]]
-	[[Category: Roberts, G C.K.]]	+	[[Category: Roberts, G C.K]]
-	[[Category: Soteriou, A.]]	+	[[Category: Soteriou, A]]
	[[Category: Inhibitor-enzyme complex]]		[[Category: Inhibitor-enzyme complex]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]

OCA at 08:10, 30 July 2014

OCA — Wed, 30 Jul 2014 08:10:33 GMT

←Older revision		Revision as of 08:10, 30 July 2014
Line 1:		Line 1:
-	[[~~Image~~:1ao8.~~png\|left~~\|200px]]	+	==DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE, NMR, 21 STRUCTURES==
		+	<StructureSection load='1ao8' size='340' side='right' caption='[[1ao8]], [[NMR_Ensembles_of_Models \| 21 NMR models]]' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1ao8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lactobacillus_casei Lactobacillus casei]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AO8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AO8 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MTX:METHOTREXATE'>MTX</scene><br>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ao8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ao8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ao8 RCSB], [http://www.ebi.ac.uk/pdbsum/1ao8 PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ao/1ao8_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We have determined the three-dimensional solution structure of the complex of Lactobacillus casei dihydrofolate reductase (18.3 kDa, 162 amino acid residues) formed with the anticancer drug methotrexate using 2531 distance, 361 dihedral angle and 48 hydrogen bond restraints obtained from analysis of multidimensional NMR spectra. Simulated annealing calculations produced a family of 21 structures fully consistent with the constraints. The structure has four alpha-helices and eight beta-strands with two other regions, comprising residues 11 to 14 and 126 to 127, also interacting with each other in a beta-sheet manner. The methotrexate binding site is very well defined and the structure around its glutamate moiety was improved by including restraints reflecting the previously determined specific interactions between the glutamate alpha-carboxylate group with Arg57 and the gamma-carboxylate group with His28. The overall fold of the binary complex in solution is very similar to that observed in the X-ray studies of the ternary complex of L. casei dihydrofolate reductase formed with methotrexate and NADPH (the structures of the binary and ternary complexes have a root-mean-square difference over the backbone atoms of 0.97 A). Thus no major conformational change takes place when NADPH binds to the binary complex. In the binary complex, the loop comprising residues 9 to 23 which forms part of the active site has been shown to be in the "closed" conformation as defined by M. R. Sawaya & J. Kraut, who considered the corresponding loops in crystal structures of complexes of dihydrofolate reductases from several organisms. Thus the absence of the NADPH does not result in the "occluded" form of the loop as seen in crystal studies of some other dihydrofolate reductases in the absence of coenzyme. Some regions of the structure in the binary complex which form interaction sites for NADPH are less well defined than other regions. However, in general terms, the NADPH binding site appears to be essentially pre-formed in the binary complex. This may contribute to the tighter binding of coenzyme in the presence of methotrexate.

-	~~{{STRUCTURE_1ao8\| PDB=1ao8 \| SCENE= }}~~	+	The solution structure of the complex of Lactobacillus casei dihydrofolate reductase with methotrexate.,Gargaro AR, Soteriou A, Frenkiel TA, Bauer CJ, Birdsall B, Polshakov VI, Barsukov IL, Roberts GC, Feeney J J Mol Biol. 1998 Mar 20;277(1):119-34. PMID:9514736<ref>PMID:9514736</ref>

-	~~===DIHYDROFOLATE REDUCTASE COMPLEXED WITH METHOTREXATE~~, ~~NMR, 21 STRUCTURES===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_9514736}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1ao8]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Lactobacillus_casei Lactobacillus casei]~~. ~~Full experimental information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=1AO8 OCA].~~	+

	==See Also==		==See Also==
	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]		*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:009514736<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Lactobacillus casei]]		[[Category: Lactobacillus casei]]